The interferons are a family of glycoproteins whose secretion from cells is induced by a number of signals including viruses, double-stranded RNAs, other polynucleotides, antigens, and mitogens. Interferons exhibit multiple biological activities, including antiviral, antiproliferative, and immunomodulatory activities. At least three distinct types of human interferons, α, β, and γ, have been distinguished based on a number of factors, including anti-viral and anti-proliferative activities.
α-interferons act through interaction with cell-surface receptors and induce the expression, primarily at the transcriptional level, of a broad but specific set of cellular genes. Several INTERFERON-induced gene products have been used as markers for the biological activity of interferons. These include, for instance, ISG15, ISG54, IRF1, GBP, and IP10.
Assays for interferon-mediated anti-viral activity have been described in the art. See, for example, McNeill, (1981) J Immunol Methods. 46:121-7. Assays for interferon antiviral activity include inhibition of cytopathic effect, virus plaque formation; and reduction of virus yield. Viral cytopathic effect assays measure the degree of protection induced in cell cultures pretreated with interferon INTERFERON and subsequently infected with viruses. See, for example, Rubinstein et al. (1981) J Virol. 37:755-8. Plaque-reduction assays can be used to measure the resistance of INTERFERON-treated cell cultures to a plaque-forming virus (for instance, measles virus). Finally, virus yield assays measure the amount of virus released from cells during, for instance, a single growth cycle. Such assays are useful for testing the antiviral activity of INTERFERONs against viruses that do not cause cytopathic effects, or that do not build plaques in target-cell cultures.
α-2b interferons have since been shown to be efficacious against viral, proliferative, and inflammatory disorders, including malignant melanoma, hairy cell leukemia, chronic hepatitis B, chronic hepatitis C, condylomata acuminata, follicular (non-Hodgkin's) lymphoma, and AIDS-related Kaposi's sarcoma. Clinical uses of interferons are reviewed in Gresser (1997) J. Leukoc. Biol. 61:567-74, and Pfeffer (1997) Semin Oncol. 24(3 Suppl 9):S9-63-S9-69.